title: A synthetic steroid 5α-androst-3β,5,6β-triol blocks hypoxia/reoxygenation-induced neuronal injuries via protection of mitochondrial function.
abstract: Ischemic stroke is a leading cause of death worldwide, yet therapies are limited. During periods of ischemia following reperfusion in ischemic stroke, not only loss of energy supply, but a few other factors including mitochondrial dysfunction and oxidative stress also make vital contribution to neuronal injury. Here we synthesized a steroid compound 5α-androst-3β,5,6β-triol by 3 steps starting from dehydroepiandrosterone and examined its effect on mitochondrial function and oxidative stress in primary cultured cortical neurons exposed to hypoxia followed by reoxygenation. 5α-Androst-3β,5,6β-triol dose-dependently protected cortical neurons from hypoxia/reoxygenation exposure. Rates of reduction in neuronal viability, loss of mitochondrial membrane potential, disruption of ATP production and oxidative stress were ameliorated in 5α-androst-3β,5,6β-triol pretreated cultures. In summary, these results suggest that 5α-androst-3β,5,6β-triol is neuroprotective against hypoxia/reoxygenation induced neuronal injuries through mediation of mitochondrial function and oxidative stress.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, PR China.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Chen
authors.forename: Tiandong
authors.initials: T
authors.lastname: Leng
authors.forename: Wenli
authors.initials: W
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Yin
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.forename: Suizhen
authors.initials: S
authors.lastname: Lin
authors.forename: Dayue
authors.initials: D
authors.lastname: Duan
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Gongxiong
authors.initials: G
authors.lastname: Wu
authors.forename: Jingxia
authors.initials: J
authors.lastname: Zhang
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000732:Androstanols; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C587859:androst-3,5,6-triol; D003687:Dehydroepiandrosterone; D000255:Adenosine Triphosphate
keywords: 5α-Androst-3β,5,6β-triol; Hypoxia/reoxygenation; Mitochondrial function; Neuroprotection; Oxidative stress